Asymmetric reduction of enoates, imines and ketones are among the most important reactions in biocatalysis. These reactions are routinely conducted using enzymes that use nicotinamide cofactors as reductants. The deazaflavin cofactor F₄₂₀ also has electrochemical properties that make it suitable as an alternative to nicotinamide cofactors for use in asymmetric reduction reactions. However, cofactor F₄₂₀-dependent enzymes remain under-explored as a resource for biocatalysis. In this review, we consider the cofactor F₄₂₀-dependent enzyme families with greatest potential for the discovery of new biocatalysts: the flavin/deazaflavin-dependent oxidoreductases (FDORs) and the luciferase-like hydride transferases (LLHTs). We discuss characterized F₄₂₀-dependent reductions that have potential for adaptation for biocatalysis, and we consider the enzymes best suited for use in the reduction of oxidized cofactor F₄₂₀ to allow cofactor recycling in situ. We also discuss recent advances in the production of cofactor F₄₂₀ and its functional analog F_O-5’- phosphate, which remains an impediment to the adoption of this family of enzymes for industrial biocatalytic processes. Finally, we discuss the prospects for the use of this cofactor and dependent enzymes as a resource for industrial biocatalysis.

Bacillus thuringiensis (Bt) is a spore-forming bacterium that produces insecticidal proteins and other virulence factors and is considered one of the most successful bioinsecticides available to control pests in agriculture. Bt strains have been reported as endophyte or rhizospheric bacteria, but little is known about the implications of this property of Bt in crop protection. Here, we review if Bt can establish as an endophyte/rhizobacterium and evaluate if Bt as an endophyte/rhizobacterium can simultaneously act against different phytopathogens (fungi, bacteria, insects and viruses) plus promote plant growth. The implications of the proposed review will broaden our understanding of Bt as a versatile entomopathogen by exhibiting differential behavior depending on context.

We propose a methodology for the quantification of model risk in the context of credit derivatives pricing and CVA, where the uncertain or unmodelled parameter is often the correlation between rates and credit. We take the rates model to be Hull-White (normal) and the credit model to be Black-Karasinski (lognormal). We show how highly accurate analytic pricing formulae, hitherto unpublished, can be derived for CDS and extended to address instruments with defaultable Libor flows which may in addition be capped and/or floored. We also consider the pricing of a contingent CDS with an interest rate swap underlying. We derive explicit expressions showing how to good accuracy the dependence of model prices on the uncertain parameter(s) can be captured in analytic formulae which are readily amenable to computation without recourse to Monte Carlo or lattice-based computation. In so doing, we take into account the impact on model calibration of the uncertain (or unmodelled) parameter.

The term “conservation,” as it relates to biodiversity in a Western context, has a storied past and as conservation science and societal values have evolved, consensus over its precise meaning has remained elusive. The broad scope of contemporary definitions hampers effective communication during a period of environmental crisis and is troublesome for any derivative concept which aims to empirically quantify the efforts of the conservation sector. This presents an avoidable hindrance to the systematic planning of the conservation field. To help remedy this situation, we provide an outcome separation framework that is based on the expected degree of separation between an action’s proximate outcome, from its intended, ultimate outcome for a habitat and/or species. Framing a definition of conservation through this lens of outcome separation allows for conservation-related actions to be clearly categorized into one of three discrete tiers: primary, secondary, and tertiary. A distillation of this tiered framework also provides a new definition of biodiversity conservation that is more rigorous and adaptable to future conceptual evolutions of the field.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

Intermittent cold exposure has garnered increased attention in popular culture, largely for its proposed effects on mood and immune function, but there are also suggestions that the energy wasting mechanisms associated with thermogenesis may decrease body weight and fat mass. Considering the continued and worsening prevalence of obesity and type II diabetes, any protocol that can reduce body weight and/or improve metabolic health would be a substantial boon. Here, we present a narrative review exploring the research related to ICE and adipose tissue. Any publicly available original research examining the effects of repeated bouts of ICE with adipose related outcomes was included. While ICE does not consistently lower bodyweight or fat mass, there does seem to be evidence for ICE as a positive modulator of the metabolic consequences of obesity, such as glucose tolerance and insulin signaling. Further, ICE consistently increases the activity of brown adipose tissue (BAT) and transitions white adipose tissue to a phenotype more in line with BAT. Lastly, the combined effects of ICE and exercise do not seem to provide any additional benefit, at least when exercise is done during ICE bouts. The majority of the current literature on ICE is based in rodent models where animals are housed in cold rooms, which does not reflect protocols likely to be implemented in humans such as cold-water immersion. Future research could specifically characterize ICE via cold water immersion in combination with controlled calorie intake to clearly determine the effects of ICE as it would be implemented in humans looking to lower bodyweight via reductions in fat mass.

Peer-to-peer (P2P) energy trading is a new data-driven business model currently being trialed within the energy sector. Introducing P2P transactions to an essential service such as energy could have far-reaching implications for individuals and the grid. This paper raises considerations and questions from social, economic/markets and regulatory points of view, that should be understood and addressed by societies and policymakers. It does this by considering under what circumstances it is reasonable to conceptualize P2P energy trading as part of the sharing economy, and drawing parallels to the sharing economy experience in other sectors. In order to reap the full societal benefits, while avoiding considerable risks to infrastructure and individuals, a policy approach promoting dialogue and innovation is necessary. We suggest the regulatory sandbox is the most appropriate tool to achieve this and would help avoid the breakdown of trust between policymakers and platform companies observed in other sectors.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

A novel compressible real gas 1D finite volume thermofluid network modelling methodology is proposed that can be applied in the analysis of supercritical CO₂ (sCO2) power cycles. It is applied to simulate centrifugal compressor performance via a mean line approach that directly solves the mass, energy, and momentum balance equations for the discretized flow channels within the machine along with the associated loss models, component characteristics, and applicable compressible real gas equation of state. This can be integrated seamlessly with the rest of the power cycle components like pipes, valves, heat exchangers, etc., thereby eliminating the need for static performance maps and the associated difficulties to ensure similarity over the whole range of operation. This direct simulation of the internal flows also makes it possible to do integrated cycle design optimization that includes the geometry of the compressors, and to simulate fast transients for dynamic analysis. The methodology was applied to simulate well-documented air and sCO2 centrifugal compressors and compared the generated results with that of conventional thermofluid network incompressible and compressible ideal gas approaches. The results indicate that the proposed compressible real gas approach can capture the stagnation pressure changes and isentropic efficiencies with good accuracy for both cases over the whole range of mass flow rates and shaft rotational speeds. In contrast, the conventional thermofluid network incompressible and compressible ideal gas approaches are only applicable in selected regions of the fluid property regime and suffer from discretization errors and inappropriate treatment of the relationship between stagnation and static pressures. Furthermore, comparative analyses between the newly proposed approach and the traditional mechanical energy balance method are performed, showing that the latter approach needs to be discretized more finely through the compression process to correctly capture the polytropic compression path shape, whereas the former more accurately captures the stagnation pressure changes through the analyzed compressors with only a single increment per compressor component.

Non-targeted effects (NTE) such as bystander effects or genomic instability have been known for many years but their significance for radiotherapy or medical diagnostic radiology are far from clear. Central to the issue are reported differences in response of normal and tumour tissues to signals from directly irradiated cells. This review will discuss possible mechanisms and implications of these different responses and will then discuss possible new therapeutic avenues suggested by the analysis. Finally, the importance of NTE for diagnostic radiology and nuclear medicine which stems from the dominance of NTE in the low dose region of the dose response curve will be presented. Areas such as second cancer induction and microenvironment plasticity will be discussed.

Power law relationships, which describe scaling relationships of data, are powerful information theoretic descriptive tools in many empirical contexts, including that of music. Zipf’s law (pink noise) describes the optimum case of a power law relation where observations are exactly inversely proportional to their rank. Descriptions that approximate a pink noise signature can be said to maximize the amount of information in a signal, and is thus suggestive of a richness of an understanding. This information density of pink noise signatures is not, however, necessarily a desirable quality for explanations in general, which, by definition, “flattens out” some data while highlighting others, ideally those most relevant to an interpretation. The privileging of data most relevant to comprehension corresponds to a red noise relationship, as opposed to the pink noise of Zipf’s law or the white noise of a description that highlights nothing in particular. Here, I explore and evaluate this concept of red noise explanations in the form of analyses of three comparable short piano works: Robert Schumann’s “Von fremden Ländern und Menschen” (no.1 from Kinderszenen op. 15, 1838), Frédéric Chopin’s Prelude op. 28 no. 20 (1838-9), and Felix Mendelssohn’s “Venetianisches Gondellied” (no. 6 from Lieder ohne Worte op. 19b, 1829-30).

On a bleak therapeutic landscape unchanged since the 1980’s, IVF with egg donation still stand as the lone medical answer to diminished reserve and premature ovarian insufficiency. Intraovarian platelet-rich plasma (PRP) crossed the horizon in 2016 as hopeful answer to these intertwined problems. The once remote mirage of platelet cytokine effects on gene regulation or telomere stabilization is now in sharper focus, and current work is clarifying how PRP corrects oxidative stress, rectifies tissue hypoxia, downregulates apoptosis, and enhances cellular metabolism. Not yet ready for routine use, this investigational treatment does offer one point of general agreement: How intraovarian PRP results should be classified—Patients are either responders or non-responders. From this, it is intriguing that no published PRP protocol has reported a supranormal ovarian rebound or hyperstimulation effect. This could be explained by baseline age-related ovarian conditions prevalent among poor responders, but since dysregulated or malignant transformations are also absent in other tissue contexts following autologous PRP treatment, the contribution of some platelet product which intrinsically delimits regenerative action cannot be discounted. Here we summarize results with recent experimental and clinical platelet research, framing those most likely to help advance reproductive endocrinology practice.

We describe an efficient and cost effective data access mechanism for Sentinel-1 TOPS 1 mode bursts. Our data access mechanism enables burst-based data access and processing, thereby 2 eliminating ESA’s Sentinel-1 SLC data packaging conventions as a bottleneck to large scale processing. 3 Pipeline throughput is now determined by available compute resources and efficiency of the analysis 4 algorithms. For targeted infrastructure monitoring studies, we are able to generate coregistered, 5 geocoded stacks of SLCs for any AOI in the world in a few minutes. In addition, we describe our 6 global scale radar backscatter and interferometric products and associated pipeline design decisions 7 that ensure geolocation consistency across the suite of derived products from Sentinel-1 data. Finally, 8 we discuss the benefits and limitations of working with geocoded SAR SLC data.

Although the statistical methods of downscaling climate data have progressed significantly, the development of high-resolution precipitation products continues to be a challenge. This is especially true when interest centres on downscaling value over several study sites. In this paper , we report a new downscaling method termed the multi-site Climate Generative Adversarial Network (MSCliGAN), which can simulate annual maximum precipitation to the regional scale during the 1950-2010 period in different cities in Canada by using different AOGCM's from the Coupled Model Inter-Comparison Project 6 (CMIP6) as input. Auxiliary information provided to the downscaling model included topography and land-cover. The downscaling framework uses a convolution encoder-decoder U-net network to create a generative network and a convolution encoder network to create a critic network. An adversarial training strategy is used to train the model. The critic/discriminator used Wasserstein distance as a loss measure and on the other hand the generator is optimized using a summation of content loss on Nash-Shutcliff Model Efficiency (NS), structural loss on structural similarity index (SSIM), and adversarial loss Wasserstein distance. Downscaling results show that downscaling AOGCMs by incorporating topography and land-use/land-cover can produce spatially coherent fields close to observation over multiple-sites. We believe the model has sufficient downscaling potential in data sparse regions where climate change information is often urgently needed.

Despite numerous studies in statistical downscaling methodology, there remains a lack of methods that can downscale from precipitation modeled in global climate models to regional level high resolution gridded precipitation. This paper reports a novel downscaling method using a Generative Adversarial Network (GAN), CliGAN, which can downscale large-scale annual maximum precipitation given by simulation of multiple atmosphere-ocean global climate models (AOGCM) from Coupled Model Inter-comparison Project 6 (CMIP6) to regional-level gridded annual maximum precipitation data. This framework utilizes a convolution encoder-dense decoder network to create a generative network and a similar network to create a critic network. The model is trained using an adversarial training approach. The critic uses the Wasserstein distance loss function and the generator is trained using a combination of adversarial loss Wasserstein distance, structural loss with the multi-scale structural similarity index (MSSIM), and content loss with the Nash-Sutcliff Model Efficiency (NS). The MSSIM index allowed us to gain insight into the model’s regional characteristics and shows that relying exclusively on point-based error functions, widely used in statistical downscaling, may not be enough to reliably simulate regional precipitation characteristics. Further use of structural loss functions within CNN-based downscaling methods may lead to higher quality downscaled climate model products.

The current plant two-sex model makes the assumption that there are only two sexual reproductive states: male and female. However, the application of this model to the plant alternation of generations requires the subtle redefinition of several common terms related to sexual reproduction, which also seems to obscure aspects of one or the other plant generation: For instance, the homosporous sporophytic plant is treated as being “asexual,” and the gametophytes of angiosperms treated like mere gametes. In contrast, the proposal is made that the sporophytes of homosporous plants are indeed sexual reproductive organisms, as are the gametophytes of heterosporous plants. This view requires the expansion of the number of sexual reproductive states we accept for plants, therefore a three-sex model for homosporous plants and a four-sex model for heterosporous plants are described and then contrasted with the current two-sex model. These new models allow the use of sexual reproductive terms in a manner largely similar to that seen in animals, and may better accommodate the plant alternation of generations life cycle than does the current plant two-sex model. These new three-sex and four-sex models may also help stimulate new lines of research, and examples of how they might alter our view of the flower, and may lead to new perspectives in terms of sexual determination, are presented. Thus it is suggested that plants have more than merely two sexual reproductive states, and that recognition of this may promote our study and understanding of plants.

This article is a followup to an earlier review which outlined some of the interesting features of the soliton/wave-action potential (AP) model, and noted the need to test its key aspects; including the need to test if its presumed lipid phase transition is actually happening during AP firings in excitable cells. The intent here is to point out the sort of tests, and evidence from them, that might be needed if the soliton/wave-AP model is to be accepted broadly by biologists. Here, after an overview of the modern electrophysiological-AP model and of the soliton/wave-AP model, there are three areas considered. First, possible compositional influences on membrane properties relative to the soliton/wave-AP model are presented. Including questions with regard to the soliton/wave-AP model’s assumption that changes in surface potentials influence the transmembrane potential. Second, some recent work from the good folks who advocate for the soliton/wave-AP model concerning the occurrence of lipid phase transitions in neurons or in extracts from nervous tissues are examined. Here it is noted that there is a need to consider whether these lipid phase transitions happen within normal physiological conditions or not. Third, and finally, the advocates for the soliton/wave-AP model have adopted a thermodynamic/theory-based philosophical approach in their studies. It is argued that this philosophical approach is a radical departure from the philosophical approach used under the scientific method. The features of this new approach, and implications its use, are examined.

Choroid plexus insufficiency or glymphatic stasis are often classified as prequels to harmful accretion of toxic proteins in neurodegenerative disease. Cognitive decline and memory loss subsequently become cardinal features of Alzheimer’s disease (AD), typically progressing with amyloid-ß and tau protein accumulation. For Parkinson’s disease (PD), α-synuclein deposits and dopamine depletion are linked to impaired movement, resting tremor, and rigidity. Importantly, both diagnoses are accompanied by hyperinflammation and intrathecal cytokine changes. Thus far, numerous clinical trials for investigational drugs have produced nothing effective for AD or PD, yet the anti-inflammatory and regenerative potential of platelet-rich plasma (PRP) remains largely unexamined in this context. This report explores a proposed Phase I study on intrathecal condensed plasma growth factors processed from autologous thrombin-activated PRP as monotherapy for AD or PD. The concept gains support from related work where cytokines of platelet origin successfully lowered inflammation, corrected background fibrosis, deactivated abnormal cells, and recovered local tissue function—all desirable outcomes in AD and PD. PRP-mediated effects on membrane potentials, electrolyte balance, and water clearance are less well characterized, but experimental evidence suggests these pathways could likewise influence glymphatic drainage to ameliorate proteinopathies. As a well-tolerated ‘orthobiologic’ with no hypersensitivity risk, intrathecal PRP and its derivatives bring advantages distinct from synthetic pharmaceuticals. If age-associated neuroinflammation in AD and PD is an upstream event contributing to neural disruption, then dampening local oxidative stress by a patient’s own platelet cytokines (as already proven in other tissues) could offer therapeutic relevance to these neurodegenerative conditions as well.

Diminished ovarian reserve can be regarded as a sentinel indicator to foreshadow severe follicular loss and, ultimately, systemic aging. The negative slope of human ovulatory fidelity begins with a robust follicular endowment which gradually declines over time. In contrast, the youthful ovarian phenotype requires the coordinated work of endothelial, granulosa, immune, perivascular, stromal and possibly germline stem cells. Such a diverse tissue matrix can, in general, be influenced by platelet (PLT)-derived factors but this has not yet been specifically confirmed in the ovary after platelet-rich plasma (PRP). How could a comparable response be validated? Here a prospective, experimental study is proposed whereby eligible patients already undergoing scheduled laparoscopy provide ovarian tissue via biopsy submitted for co-culture with autologous Ca⁺² activated PRP. Recognizing the interlocking, central roles of nuclear factor κB (NF-κB) and tumor necrosis factor-α (TNF-α), incubated samples would be assessed for these in vitro before vs. after PRP exposure, in addition to stereomicroscopy. A mathematical model is available to track NF-κB oscillations and estimate gene expression, cell development, growth, apoptosis, and key immune and inflammatory actions. Since NF-κB and TNF-α are discharged in activated PLT releasate (or react to its cargo proteins) this audit permits extraction of response markers observed post-stimulus, thus linking discrete signals to transcriptional output, cellular fitness, and ovarian cytoarchitecture. From this, a hypothesis could emerge where intraovarian PRP is found to make no direct impact on follicles, although modified ovarian field function and curtailed local entropy incidentally favor optimized oocyte competence as a secondary effect.

Abstract: This paper summarises an early and successful piece of citizen science, performed within The University of Queensland Seismograph Stations (UQSS) observatory, in cooperation with colleagues at CSIRO. It was designed to en-courage young STEM students from Brisbane high schools to engage in “real” re-search, back in 1995. Having completed the project report, their (analog) results sat in a cupboard until the report was dusted off and the project was re-analysed in 2022 by an honors student, considering timely climate change applications for the study. This is a time when science is changing considerably from analog to digital medium and operational methods. The original project was called Earthquake generated T phases on BRS Seismograph (Brisbane, Q’ld)- a predictor for Tasman Sea Tsunamis? [1] Fortunately, seismology is a very collaborative field. The research question has since changed. There is a lot of data analysis involved in the science of recording earthquake signals, with auxiliary definitive catalogues, observers logbooks, housing of the recordings themselves (analog and digital) and the software mediums that change over time. In other words, a lot of headaches can be encountered in longitudinal data collection study such as this. The citizen science students used a pre-prepared decadal collection (1980-90) derived from the BRS observatory data catalogue. BRS is part of the global World-Wide Seismograph Station Network (WWSSN). Currently in Australia, university earth science observatories have diminished, and in their place, public seismic networks (PSN) have evolved, either in back-yard sheds or school science labs. The level of expertise required fits the role of advancing citizen science for a real science advantage. This is a topical citizen disaster preparedness action area for today’s climate emergency, which is threatening the globe and all lifeforms. Citizen engagement or mobilisation is an essential preparedness strategy. Keywords: citizen science 1; seismology 2; earth observation 3; climate change 4; education for sustainable development 5; disaster preparedness 6; disaster alerts 7

Abstract: The contribution of breakfast to diet quality (DQ) can inform future dietary guidelines. This study examined breakfasts that were associated with highest-quality diets. Dietary data came from the first reported day of the National Health and Examination Survey (NHANES) 2011-2014 (n=14,488). DQ measures were the Nutrient Rich Foods Index (NRF9.3) and the USDA Healthy Eating Index 2015 (HEI 2015). Analyses of breakfast intakes were conducted by NRF9.3 tertiles and by age and socioeconomic groups. Four out of 5 NHANES participants ate breakfast. Breakfast provided 19-22% of dietary energy depending on age. Breakfast intakes of complex carbohydrates and total sugars were higher and intakes of protein and fats were lower relative to energy intakes. Breakfast provided more that 20% of daily intakes of B vitamins, vitamins A and D, folate, calcium, iron, potassium and magnesium. Eating breakfast was associated with higher NRF9.3d scores. Breakfasts associated with top tertile of NRF9.3d had more carbohydrates and less added sugars and fats. Such breakfasts had more fruit and juices, more whole grains, more milk and yogurt and less meat and eggs. Breakfast patterns that favored fruit, whole grains, and dairy were associated with healthiest diets.

Remote sensing technologies are critical for analyzing the escalating impacts of global climate change and increasing urbanization, providing vital insights into land surface temperature (LST), land use and cover (LULC) changes, and the identification of urban heat island (UHI) and surface urban heat island (SUHI) phenomena. This research focuses on the nexus between LULC alterations and variations in LST and air temperature (Tair), with a specific emphasis on the intensified SUHI effect in Kharkiv, Ukraine. Employing an integrated approach, the study analyzes time-series data from Landsat and MODIS satellites, alongside Tair climate records, utilizing machine learning techniques and linear regression analysis. Key findings indicate a statistically significant upward trend in Tair and LST during summer months from 1984 to 2023, with a notable positive correlation between Tair and LST across both datasets. MODIS data exhibit a stronger correlation R² = 0.879, compared to Landsat R² = 0.663. The application of supervised classification through Random Forest algorithms and vegetation indices on LULC data reveals significant alterations, manifested as a 70.3% increase in urban land, concurrently with a decrement in vegetative cover, especially 15.5% reduction in dense vegetation and a 62.9% decrease in sparse vegetation. Change detection analysis elucidates a 24.6% conversion of sparse vegetation into urban land, underscoring a pronounced trajectory towards urbanization. Temporal and seasonal LST variations across different LULC classes were analyzed using kernel density estimation (KDE) and boxplot analysis. Urban areas and sparse vegetation had the smallest average LST fluctuations, at 2.09°C and 2.16°C, respectively, but recorded the most extreme LST values. Water and dense vegetation classes exhibited slightly larger fluctuations of 2.30°C and 2.24°C, with the bare land class showing the highest fluctuation 2.46°C, but fewer extremes. Quantitative analysis with the application of Kolmogorov-Smirnov tests across various LULC classes substantiated the normality of LST distributions p > 0.05 for both monthly and annual data sets. Conversely, the Shapiro-Wilk test validated the normal distribution hypothesis exclusively for monthly data, indicating deviations from normality in the annual data. Thresholded LST classifies urban and bare lands as warmest classes with 39.51°C, 38.20°C and water by 35.96°C and dense vegetation 35.52°C, sparse vegetation 37.71°C as coldest, a trend consistent annually and monthly. The analysis of SUHI effects demonstrates an increasing trend in UHI intensity, with statistical trends indicating a growth in average SUHI values over time. This comprehensive study underscores the critical role of remote sensing in understanding and addressing the impacts of climate change and urbanization on local and global climates, emphasizing the need for sustainable urban planning and green infrastructure to mitigate UHI effects.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

The Ballynoe barite deposit is a conformable, mineralized horizon of Lower Carboniferous age overlying a diastem and mass faunal extinction demarking the transition from a quiet water environment to one of dynamic sedimentation. The geometry of the barite orebody correlates with the palaeo-topography of the footwall, which acted as an important control over the lateral extent, thickness and nature of the mineralization. Sedimentary features within the barite horizon suggest that it was precipitated in the form of a cryptocrystalline mud which underwent major diagenetic modification resulting in extensive stylolitisation, recrystallisation and remobilization. There is abundant and compelling geological and isotopic evidence for early local exhalation from the presence of a hydrothermal vent fauna consisting of a delicately pyritized worm tubes hosted and haematized filaments of apparent microbial origin. The worm tubes are remarkably similar to examples from modern and ancient volcanic-hosted massive sulphide deposits, and the filamentous microfossils have similarities to modern Fe-oxidizing bacteria. Strontium in the barite has a 87Sr/86Sr ratio indistinguishable from sea-water between 350 and 344Ma whilst oxygen isotopes from barite and chert suggest a diagenetic origin in equilibrium such sea-water around 60-70°C. Fluid inclusion studies have shown that, in general, low temperature inclusions are very saline (20-25%) whilst at higher homogenization temperatures they are more dilute (9-12%).

A view of life, based on sympoiesis, metabolism, and the second law of thermodynamics is proposed. Sympoiesis is the notion that organisms develop as teams, and that symbionts play roles in forming their partners. Metabolism is seen to occur not only within these developmental symbionts, but between them, as well. This occurs through thermodynamic principles of finding the lowest free energy states. Once one accepts the thermodynamics of metabolism and that holobionts emerge through sympoiesis, Gaia becomes readily understood. New ethical principles flow from these considerations.

Drawing inspiration from a recent construction of a polyhedral structure associated with an icosahedrally-symmetric map on the Riemann sphere, the article shows how to build such "dynamical polyhedra" for other icosahedral maps. First, icosahedral algebra is used to determine a special family of maps with 60 periodic critical points. The topological behavior of each map is worked out and results in a geometric algorithm that constructs a system of edges---the dynamical polyhedron---in natural correspondence to a map's topology. It turns out that the maps' descriptions fall into classes the presentation of which concludes the paper.

We describe a forecast system based on the Weather Research and Forecasting (WRF) model for the prediction of high-impact weather events affecting power utilities, particularly conditions conducive to wildfires. The system was developed for Pacific Gas and Electric Corporation (PG&E) to operationally forecast conditions in Northern and Central California. It was established in 2014 and has been periodically improved. In the current configuration, WRF forecasts are routinely performed multiple times each day on a 2-km grid, and the results are used as input to wildfire fuel moisture, fire probability, and wildfire spread models. Components of the system include a stochastically perturbed ensemble; an annually updated reanalysis covering more than 30 years; and validation against PG&E’s extensive mesonet and other observing networks. We describe the development and validation of the next operational edition. Configurations tested include irrigation triggered by crop growing season and an ensemble-based approach with intelligently sub-selected Global Ensemble Forecast System (GEFS) members. The latter approach allows for enhanced uncertainty sampling in WRF forecasts and can greatly improve WRF forecasts when calibrated by observations.

The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, spurring the development of new frameworks through epidemiological studies. Traditionally, each individual was thought to harbor unique microbial communities acquired early in life, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.

Recent times have witnessed an increasing number of countries and private firms pledging carbon neutrality by mid-century. Whilst representing a significant improvement in intentions to tackle climate change, such pledges lack substance and structure. For instance, individual pledges lack coordination and aggregation among peers, while strategies and measures to achieve ambitious targets are largely absent. Moreover, current disagreements obstructing progress in international climate change negotiations further undermine the reliability of carbon neutrality objectives. Effective international policies are needed to foster aggregate mitigation ambitions and the creation of adequate supporting mechanisms. This theoretical paper describes a governance innovation aimed at overcoming such shortfalls and disagreements through a unifying yet customizable pathway towards carbon neutrality. It does so by first outlining a political governance framework based on a climate club interpretation of Article 6 of the Paris Agreement. Secondly, it proposes carbon emission mitigation effort sharing on a per capita basis to ensure efficiency, equity and political feasibility. Thirdly, this paper describes how the supply of certified mitigations of carbon emissions required to satisfy effort sharing-based demand can be assetized as carbon credits by operationalizing Article 6 as a joint certification mechanism. The resulting governance architecture for managing demand and supply of mitigations shifts efforts to tackle climate change from a ‘problem-driven’ cost approach to ‘opportunity-driven’ value creation pathways towards carbon neutrality.

Recently, the properties of bouncing oil droplets, also known as `walkers', have attracted much attention because they are thought to offer a gateway to a better understanding of quantum behaviour. They indeed constitute a macroscopic realization of wave-particle duality, in the sense that their trajectories are guided by a self-generated surrounding wave. The aim of this paper is to try to describe walker phenomenology in terms of de Broglie-Bohm dynamics and of a stochastic version thereof. In particular, we first study how a stochastic modification of the de Broglie pilot-wave theory, à la Nelson, affects the process of relaxation to quantum equilibrium, and we prove an H-theorem for the relaxation to quantum equilibrium under Nelson-type dynamics. We then compare the onset of equilibrium in the stochastic and the de Broglie-Bohm approaches and we propose some simple experiments by which one can test the applicability of our theory to the context of bouncing oil droplets. Finally, we compare our theory to actual observations of walker behavior in a 2D harmonic potential well.

We describe an efficient approach to radiometrically flatten geocoded stacks of calibrated synthetic aperture radar (SAR) data for terrain-related effects. We use simulation to demonstrate that, for the Sentinel-1 mission, one static radiometric terrain flattening factor derived from actual SAR imaging metadata per imaging geometry is sufficient for flattening interferometrically compliant stacks of SAR data. We quantify the loss of precision due to application of static flattening factors, and show that these are well below stated requirements of change detection algorithms. Finally, we discuss the implications of applying radiometric terrain flattening to geocoded SAR data instead of the traditional approach of flattening data provided in the original SAR image geometry. The proposed approach allows for efficient and consistent generation of five different Committee of Earth Observation Satellites (CEOS) Analysis Ready Dataset (ARD) families - Geocoded Single Look Complex (GSLC), Interferometric Radar (InSAR), Normalized Radar Backscatter (NRB), Polarimetric Radar (POL) and Ocean Radar Backscatter (ORB) from SAR missions in a common framework.

This paper presents a parametric study of the multistorey hydro-powered pump, known as "Bunyip," which has demonstrated significant potential in contributing to rural regions. The study aims to understand the underlying physics of the system and enhance its hydraulic performance. A transient three-dimensional model using the commercial Computational Fluid Dynamics (CFD) tool Ansys-Fluent is utilized to gain insights into the fundamental flow mechanics, operational efficiency, standard capacity, and relative delivery. The investigation involves an initial assessment of performance for three Bunyip devices based on manufacturing data. Parametric analysis is conducted, and a parametric dataset is generated through meticulous application and numerical modelling. The CFD results are validated against experimental data. Three design configurations are considered, and 58 sets of varied input parameters are examined. The best design configuration is evaluated against five cases of conventional hydro-power pump systems. The results indicate that a smaller diameter of the pressure chamber and a higher supply head lead to higher pressure, achieving a target head of 3 m with 15% efficiency and a flowrate of 11.82 l/min.

The aim of this paper is to examine the beneficial impact of feedback information in the dynamics of production-inventory control systems. Two production-inventory control system models are analyzed: APIOBPCS and 2APIOBPCS models. The simulation-based experiment designs were conducted by using the state-space equations of the two models. The bullwhip effect as measured by the variance ratio between the order rate and the consumption rate, and inventory responsiveness as measured by the Integral of Absolute Error between the actual and the target levels of inventory, are two metrics used to evaluate the performance of the production-inventory control system in response to a random customer demand. To ensure that both models work under optimal performance, multi-objective particle swarm optimization (MOPSO) is employed to address the problem of tuning the controller’s parameters. The simulation results show the 2APIOBPCS model outperforms the APIOBPCS model at achieving the desired bullwhip effect and being able to provide better inventory responsiveness. The improvement in the inventory responsiveness becomes more significant when the system operates under mismatched lead time and/or an initial condition.

Platelets are a uniquely mammalian physiologic attribute. As the only non-marine vertebrate class to experience menopause, humans have a substantial post-reproductive lifespan and are believed to have a limited, non-renewable oocyte supply. Ovarian reserve typically declines after about age 35yrs, marking losses which cannot be recovered by available fertility medications. When in vitro fertilization fails due to low or absent ovarian response, gonadotropin adjustments are often ineffectual and if additional oocytes are occasionally harvested, egg quality is usually poor. This problem was confronted by Greek researchers who developed a new surgical method to insert autologous platelet-rich plasma (PRP) into ovaries; the first ovarian PRP success to improve reproductive outcomes was published from Athens in 2016. This innovation influenced later research with condensed platelet-derived growth factors, leading to correction of oocyte ploidy error, normal blastocyst development, and additional term livebirths. Yet women’s health was among the last clinical domains to explore PRP, and its role in ‘ovarian rejuvenation’ remains unsettled. One critical aspect in this procedure is platelet activation, a commonly overlooked step in the cytokine release cascade considered essential for successful transition of undifferentiated ovarian stem cells to an oocyte lineage. Poor activation of platelets thus becomes an unforced error, potentially diminishing or even negating post-treatment ovarian follicular response. To answer this query, relevant theory, current disagreements, and new data on platelet activation are presented, along with clinical challenges for regenerative fertility practice.

Sterile alpha motif domain-containing protein 9 (SAMD9) is a regulatory protein centrally involved in cell proliferation and apoptosis. Mapped to 7p21.1, variants in SAMD9 have been reported in <50 pediatric cases worldwide, typically with early lethality. Germline gain-of-function SAMD9 variants are associated with MIRAGE Syndrome (myelodysplasia, infection, restricted growth, adrenal hypoplasia, genital anomalies, and enteropathy). Spalt like transcription factor 1 (SALL1) is a zinc finger transcriptional repressor located at 16q12.1 where only two transcript variants in SALL1 are known. RUNX2 (6p21.1) encodes a nuclear protein with a Runt DNA-binding domain critical for osteoblastic differentiation, skeletal morphogenesis, and serves as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. RUNX2 and SALL1 are thus both ‘master regulators’ of tissue organization and embryo development. Here, we describe exome sequencing and copy number variants in two previously unknown mutations—R824Q in SAMD9, and Q253H in SALL1. A new multiexon 3’ terminal duplication in RUNX2 is also reported. This is the first known phenotype characterization for the intersection of all three variants in a healthy 46,XX adult. Focusing on developmental progress, ultrastructural renal anatomy, and selected reproductive aspects, we describe this unique genotype diagnosed incidentally during Covid-19 illness. Individual disruption in SAMD9, RUNX2, or SALL1 would be expected to give a bleak prognosis. However, the convergence discovered here appears to dampen severe pathology, perhaps by cross-gene silencing of effects normally deleterious when such changes occur alone.

The selection of biomaterials for biomedical application is a significant challenge. In the last few decades, various bioabsorbable and stable biopolymers have been applied for use as biomedical devices in orthopedic applications. Ultra-high molecular weight polyethylene (UHMWPE) has been extensively used in medical implants, notably in the bearings of hip, knee, and other joint prostheses, owing to its biocompatibility and high wear resistance. For the ACL graft, synthetic UHMWPE is an ideal candidate due to its biocompatibility and its extremely high tensile strength. Despite the appeal of new advanced materials such as carbon fiber, poly-ether-ether ketone, and other load-bearing materials, UHMWPE remains a primary load-bearing candidate material for ACL reconstructions because of its extremely high strength, the simplicity of the fabrication process, its biocompatibility, and low friction. However, some significant problems are observed in UHMWPE based implants, such as wear debris, and oxidative degradation due to the generation of free radicals when exposed to irradiation with gamma rays for grafting or sterilization. Various innovative methodologies have been developed to resolve those problems and enhance the properties of UHMWPE. In this review, we will explore in detail the methods for surface functionalization of UHMWPE and will apply these findings to the case study of UHMWPE for Anterior Cruciate Ligament repair.

The first published description of intraovarian platelet-rich plasma (PRP) appeared in mid-2016, when a new experimental technique was successfully used in adult human ovaries to correct the reduced fertility potential accompanying advanced maternal age. Considering the potential therapeutic scope of intraovarian activated PRP and/or condensed platelet cytokines would likely cover both menopause treatment and infertility, the mainstream response has ranged from skeptical disbelief to welcome astonishment. Indeed, reports of restored menses in menopause (as an alternative to conventional hormone replacement therapy) and healthy term livebirths for infertility patients (either with IVF or as unassisted conceptions) after intraovarian PRP injection continue to draw notice. Yet any proper criticism of ovarian PRP applications will be difficult to rebut given the heterogenous patient screening, varied sample preparations, wide differences in platelet incubation and activation protocols, surgical/anesthesia techniques, and delivery methods. Notwithstanding these features, no adverse events have been reported thus far and ovarian PRP appears well tolerated by patients. Here, early research guiding the transition of ‘ovarian rejuvenation’ from experimental to clinical is outlined. Likely mechanisms are presented to explain results observed in both veterinary and human ovarian PRP research. Current and future challenges for intraovarian cytokine treatment are also discussed.

Apoptosis is associated with numerous phenotypical characteristics, and is thus studied with many tools. In this study, we compared two broadly used apoptotic assays: TUNEL and staining with an antibody targeting the activated form of an effector caspase. To compare them, we developed a protocol based on commonly used tools such as filters, zprojection and thresholding. Even though it is commonly used in imageprocessing protocols, thresholding remains a recurring problem. Here we analyzed the impact of processing parameters and readout choice on the accuracy of apoptotic signal quantification. Our results show that TUNEL is quite robust, even if image processing parameters can allow or not to detect subtle differences of the apoptotic rate. On the contrary, images from anticleaved caspase staining are more sensitive to handle and proved to necessitate to be processed more carefully. We then developed an open source Fiji macro automatizing most steps of the image processing and quantification protocol. It is noteworthy that the field of application of this macro is wider than apoptosis as it can perfectly be used to treat and quantify other kind of images.

The quality of dietary patterns can be optimized using a mathematical technique known as linear programming (LP). LP methods have rarely been applied to individual meals. The present LP models optimized the breakfast meal for those participants in the nationally representative National Health and Nutrition Examination Survey 2011-2014 who ate breakfast (n=11,565). The Nutrient Rich Food Index (NRF9.3) was a measure of diet quality. Breakfasts in the bottom tertile of NRF9.3 scores (T1) were LP-modeled to meet nutrient requirements without deviating too much from current eating habits. Separate LP models were run for children and for adults. The LP-modeled breakfasts resembled the existing ones in the top tertile of NRF9.3 scores (T3), but were more nutrient-rich. Favoring fruit, cereals, and dairy, the LP-modeled breakfasts had less meat, added sugars and fats but more whole fruit and 100% juices, more whole grains, and more milk and yogurt. LP modeling methods can build on existing dietary patterns to construct food-based dietary guidelines and identify individual meals and/or snacks that need improvement.

Transitioning to clean cooking fuels is not only part of achieving SDG7, but also makes a significant contribution to mitigating climate change by reducing carbon emissions. The paper contradicts the conventional wisdom that electricity is too expensive to cook with. The paper explores the energy required to cook dishes using different technologies and fuels by analysing data from Cooking Diaries and Controlled Cooking tests conducted under the MECS programme. Electric pressure cookers (EPCs) use least energy when compared with electric hotplates, and a detailed description of how the EPC works explains why this should be. The paper draws out distinctions between African and Asian dishes, notably the impact of energy intensive dishes prepared mostly in Africa. Standard efficiency based approaches to comparing the performance of stoves are not appropriate to modern electric cooking devices so an alternative approach based on specific energy consumptions is proposed e.g. charcoal stoves use 15 times as much energy as EPCs to cook African dishes. Energy ratios provide a basis for estimating carbon emission reductions associated with transitioning to modern cooking fuels. Historical costs show that the cost of cooking with an EPC can be only 20% of the cost of cooking with charcoal, which highlights the potential for modern, energy efficient electric cooking devices to defy the conventional wisdom of the energy ladder.

The problem can be stated as over 3 billion choices to improve 14 disease states with 9 optimization goals (some of the optimization goals are diametrically opposed) to improve dyspnea, shortness of breath, fatigability, exercise intolerance, edema, swelling, fluid retention, and arrhythmias. The goal is to increase Left Ventricular Outflow Integral, reduce mitral regurgitation, increase longitudinal conduction velocities and restore synchrony of the septum to the ventricle that needs it the most. A method to accomplish this task for the spectrum of cardiac disease is presented.

Human decision-making is increasingly supported by artificial intelligence (AI) systems. From medical imaging analysis to self-driving vehicles, AI systems are becoming organically embedded in a host of different technologies. However, incorporating such advice into decision-making entails a human rationalization of AI outputs for supporting beneficial outcomes. Recent research suggests intermediate judgments in the first stage of a decision process can interfere with decisions in subsequent stages. For this reason, we extend this research to AI-supported decision-making to investigate how intermediate judgments on AI-provided advice may influence subsequent decisions. In an online experiment (N=192), we found a consistent bolstering effect in trust for those who made intermediate judgments and over those who did not. Furthermore, violations of total probability were observed at all timing intervals throughout the study. We further analyzed the results by demonstrating how quantum probability theory can model these types of behaviors in human-AI decision-making and ameliorate the understanding the interaction dynamics at the confluence of human factors and information features.

What drives an individual police officer to activate his body-worn camera (BWC)? Some evidence suggests officer attitudes and resistance to the technology contributes to the equivocal results in studies testing for BWCs effect on use-of-force, complaints, and other outcomes of interest. Leveraging a novel survey and administrative dataset, we investigate the predictors of BWC activation among 147 police officers in a single agency. With a test of three nested models, we find job function covariates offer robust predictive power of how often an officer activates her or his BWC. Neither demographic nor attitudinal measures significantly predict BWC activations, except for a negative relationship with how officers perceive BWC impacts on professional discretion. The study furnishes empirical support for understanding officers as Principled Agents: job function, guided by administrative policy is the most explanatory and parsimonious, while models of attitudes and demographics fail to improve upon the job function model.

The 2015 Dietary Guidelines for Americans recommends that individuals should eat as little dietary cholesterol as possible. However, current dietary cholesterol intake and its food sources have not been well-characterized. We examined dietary cholesterol intake by age, sex, race, and food sources using 24-hour dietary recall data from a nationally representative sample of 5047 adults aged 20 years or older who participated in NHANES (2013–2014 survey cycle). We also reported trends in cholesterol intake across the past 7 NHANES surveys. Mean dietary cholesterol intake was 293 mg/day (348 mg/day for males and 242 mg/day for females) in the 2013–2014 survey cycle; 39% of adults had dietary cholesterol intake above 300 mg/day (46% for males and 28% for females). Meat, eggs, grain products, and milk were the highest four food sources of cholesterol, contributing to 96% of the total consumption. Both average cholesterol intake and food source varied by age, sex, and race (each p < 0.05). Mean cholesterol intake of the overall population had been relatively constant at ~290 mg/day from 2001–2002 to 2013–2014 (p-trend = 0.98). These results should inform public health efforts in implementing dietary guidelines and tailoring dietary recommendations.

This research investigates the relationship among human knowledge, behavior, and risk as they relate to urban chicken husbandry in the U.S. Concern over zoonotic diseases has been on the rise, especially with increasing contact. In particular, avian influenza, or bird flu, Salmonella enterica (salmonella), and Escherichia coli (E. coli), can all cross species lines between people and poultry. This study analyzed knowledge and practices in urban chicken husbandry to assess how they relate to risk of disease acquisition, hypothesizing that certain practices associated with a lessened knowledge base may heighten the risk. This study used social surveys to examine the self-reported knowledge base of individuals involved in chicken husbandry as they relate to beliefs and behaviors associated with the care of these animals. These results identify key factors that may heighten the risk of disease transmission, and demonstrate that an increased knowledge base could act to lessen this risk.

Geijera Schott is a plant genus of the Rutaceae Juss. (rue and citrus) family, comprising six species which are all native to Oceania. Of the plants belonging to this genus, the most significant species that has a customary use is Geijera parviflora, which was used by Indigenous Australians, primarily as a pain reliever. Herein, a comprehensive review of the literature published on the genus Geijera from 1930-2023 was conducted. This is the first review for this plant genus and it highlights the chemical constituents reported to date, together with the range of pharmacological properties described from the various species and different parts of the plant. These properties include anti-inflammatory, anti-microbial, anti-parasitic, insect repellent, analgesic, neuroactive, and anti-cancer activities. Finally, a reflection on some of the important areas for future focused studies of this plant genus is provided.

Unlike trees, shrubs (i.e., multiple-stemmed woody plants) do not need evenly spaced large diameter structural roots and thus can spread further per unit belowground biomass. We therefore hypothesized that compared to trees, shrubs respond more to asymmetric distributions of nutrients and reach nutrient-rich patches of soil faster and with less below-ground biomass. To test these hypotheses we planted individual seedlings of shrubs (Cornus racemosa, Rhus glabra, and Viburnum dentatum) and trees (Acer rubrum, Betula populifera, and Fraxinus americana) in the centers of sand-filled rectangular boxes. In one direction we created stepwise gradients of increasing soil nutrients with slow-release fertilizer; in the other direction no fertilizer was added. Seedlings were harvested when their first root reached the plexiglass-covered fertilized end of their box; time taken as well as above- and below-ground biomass by nutrient segment were determined. There were no consistent differences between the shrubs and trees in belowground architectural plasticity (= ratio of biomass in fertilized and unfertilized volumes of soil) or in the rate and efficiency of lateral growth. Interspecific variation appeared more related to edaphic characteristics of the native habitats than to growth form. The fastest and most efficient roots were produced by the shrub (R. glabra) and the tree (B. populifolia) that are characteristic of poor soils. Root foraging by R. glabra was also facilitated by rapid rhizomatous expansion. The tested shrubs and trees did not consistently differ in nutrient foraging efficiencies or rates but further study is warranted with larger plants and more species.

This paper outlines the evolution of a learning technology interface from a Beta version to launch with educators and its alignment to pedagogical theory, designed to maximise collaboration between teacher and student. It explores how the “co-creation” of curricula via textual sources that underpin teaching and learning can be enhanced through interactive e-books and outlines the challenges involved in this praxis. With a number of stakeholders involved in the live use of the platform (including teachers, students, HE educators, course instructors, curriculum designers and software developers), iterative feedback loops informed real-time design improvements to both the interface and the-ory. This collaboration utilised a design-based research (DBR) approach (Wang and Hannafin, 2005), which is outlined here as explanation of how the tool developed and how iterative feedback helped to reconsider the challenges educators face in implementing pedagogical innovation across differing contexts. We propose how speculative design (Lukens and DiSalvo, 2012) and Activity Theory (Engeström, 1987) workshops can methodologically enhance the planning and evaluation phases inherent to DBR approaches, which involve students to prepare for educators’ innovation. Finally, we conclude with how educators can utilise these design principles using stratified approaches to help prepare organisational approaches for innovation.

Greenhouse Gases (GHG) emissions from dairy farms are significant contributors to global warming. However much of the published work on GHG reduction is focused on either Methane (CH4) or Nitrous Oxide (N2O), with few, if any, considering the interactions that changes to farm systems can have on both gases. This paper takes the raw data from a year of activity on a 300 cow commercial dairy farm in Northern Ireland to more accurately quantify the GHG sources by use of a simple predictive model based on IPCC methodology. Differing herd management policies are examined together with the impact of integrating Anaerobic Digestion (AD) into each farm system. Whilst significant success can be predicted in capturing CH4 and Carbon Dioxide (CO2) as biogas and preventing N2O emissions, gains made can be lost in a subsequent process negating some or all of the advantage. The process of extracting value from the captured resource is discussed in the light of current farm parameters together with indications of other potential revenue streams. However, this study has concluded that despite the significant potential for GHG reduction, there is little incentive for widespread adoption of manure based farm scale AD in the UK at this time.

This paper examines cognitive biases which affect the ability of decision makers to make rational decisions in an organizational context. The motivation for this analysis begins with the observation of catastrophic accidents caused by human error but in an organizational context. This paper expands on the concept of cognitive bias to define organizational biases which are the factors that affect decisions in an organizational context. The paper distinguishes between organizational biases, which are the focus of this paper, and individual biases, which are biases experienced by individuals but may have organizational consequences. The purpose of this paper is to identify methods to mitigate the risks of organizational accidents, accidents which involve many people operating at different levels of an organization. The methodology is to identify those decisions that would address the specific organizational biases. The focus of this paper is the decisions for mitigating the risks associated with decisions in an organizational context. Results are shown for seven organizational biases, six specific case studies, and four decision options. This paper concludes that organizational biases are intrinsically different from individual biases and that these differences lead to different decision options from those that mitigate individual biases; however, they may exist concurrently.

Despite constituting the western-most edge of the population distributions for several native European flora, Ireland has largely been left out of key Europe-wide phylogeographic studies. This is true for birch (Betula pubescens Ehrh. and Betula pendula Roth.), for which the genetic diversity has yet to be mapped for Ireland. Here, we used eight cpDNA (two RFLP and six SSR) markers to map the genetic diversity of B. pubescens, B. pendula and putative hybrid individuals sampled from 19 populations spread cross most of the island of Ireland. Within Ireland, 11 distinct haplotypes were detected, the most common of which (H1) was also detected in England, Scotland, France and Norway. A moderate level of population structuring (GST = 0.282) was found across Ireland and the genetic diversity of its northern populations was twice that of its southern populations. This indicates that, unlike other native Irish trees, such as oak and alder, post-glacial recolonisation by birch did not begin in the south (i.e., from Iberia). Rather, and in agreement with palynological data, birch most likely migrated in from eastern populations in Britain. Finally, we highlight Irish populations with comparatively unique genetic structure which may be included as part of European genetic conservation networks.

This manuscript offers a concise overview of paper microfluidics, emphasizing its sustainable sensing applications in healthcare, environmental monitoring, and food safety. Researchers have developed innovative sensing platforms for detecting pathogens, pollutants, and contaminants by leveraging the paper’s unique properties, such as biodegradability and affordability. These portable, low-cost sensors facilitate rapid diagnostics and on-site analysis, making them invaluable tools for resource-limited settings. The review discusses fabrication techniques, principles, and applications of paper microfluidics, showcasing its potential to address pressing challenges and enhance human health and environmental sustainability.

Vacuum pump wear is the most prevalent failure mode of the IBA Synthera® automated radiochemistry system. Rebuilding or replacing the pump causes equipment downtime and increases the radiation exposure of the service personnel. We built a dedicated test device to assess new or rebuilt pumps prior to installation, thus reducing downtime and radiation exposure during repairs. The Testbed incorporates a microprocessor that actuates the pump, valves, pressure sensor, and communicates with the user through lights, buttons, and an alphanumeric screen. The Testbed increases productivity and safety in the radiochemistry laboratory.

Perforating dermatoses are dermatologic disorders with transepidermal elimination (TE) of dermal substances. While TE is typically associated with collagen and elastin, it can also occur as a secondary event in other processes, and it is important to keep a broad differential. We present a case of perforating tophaceous gout, which underscores the need for a thoughtful approach to perforating disorders. An updated review of recent literature is also presented.

We report on ground-based measurements of the atmospheric electric field (Ez= -Potential Gradient (PG)) and current density (Jz) that were conducted at two locations in Israel. One is the Emilio Segre cosmic ray station located on Mt. Hermon (34.45 N, 2020 m AMSL) located in northern Israel near the Syrian-Lebanon border and at the other at the Wise astronomical observatory in the Negev desert highland plateau of southern Israel (31.18 N, 870 m AMSL). We searched for possible effects of strong, short-term solar events on the potential gradient and the vertical current density, as disruption to the Global Electric Circuit are often observed following strong solar events. The first case study (St. Patrick Day, 17 March 2015) was classified as the strongest event of 2015. The second case study (8 Sep 2017) was categorized as the strongest event of 2017 and one of the twenty strongest events on record to date. The results show that the electrical parameters measured at ground level at both stations were not affected during the two massive proton events and the ensuing geomagnetic storms. The magnetospheric shielding in lower latitudes is strong enough to shield against flux of energetic particles from solar events, obscuring any impact that may be noticeable above the local daily variations induced by local meteorological conditions (aerosol concentrations, clouds, high humidity, and wind speed) which were investigated as well.

Background: Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will take HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of negative HRT health effects from extended use has piqued interest in ‘safer options’. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. Methods: HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. Results: Mean±SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about USD 576±246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean±SD cost for OPRP at USD 8,710±4,911/yr (p<0.0001 vs. HRT, by t-test). Upper-bound estimates for annual HRT and OPRP costs were USD 1,341 and USD 22,232, respectively. Conclusions: While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT currently available.

The ecosystem plays a crucial role in mitigating climate change and protecting the environment. This study employs GIS technology to conduct an in-depth analysis of the current status of Queensland's ecosystem and develops a Climate Change Vulnerability Index (CCVI) model based on six sub-factors. These sub-factors include the Exposure Index (Mean surface temperature and precipitation), the Sensitivity Index (Population density, Building density, and Proximity to forests and nature reserves), and the Adaptive Capacity Index (Nighttime light radiation). The findings indicate that the CCVI value is lowest in the southeastern coastal region of Queensland, suggesting that this area is less vulnerable to climate change. However, other coastal areas and the far western inland regions exhibit higher CCVI values, indicating greater climate vulnerability. These areas require attention and the implementation of appropriate measures. By deepening our understanding of exposure, sensitivity, and adaptive capacity, we can formulate effective policies and measures to promote sustainable development and mitigate the negative impacts of climate change on the region. This study holds significant practical implications for guiding ecological planning and management decisions in the area.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

As a result of the cancer immunotherapy revolution hundreds of clinical trials of the newly approved immunotherapies are now under way to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by blockade of co-inhibitory signals. While success stories of terminal cancer patients achieving complete remissions are accumulating, not enough research has been done into the risks of the new therapies. Since the use of immunotherapy is becoming more common, and is expected to develop into first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the nemesis of immunotherapy. Immune-related adverse events (IrAEs) could affect any tissue, their incidence may reach up to 90% of patients and toxicity is dose-dependent. While the combination of two immune checkpoint inhibitors (ICIs) increased efficacy, the incidence of severe adverse events was also increased. Apparently, ICIs cannot be restricted to the targeted anti-tumor T cell population. The long lasting objective of cancer regression can only be achieved by paying a price: tolerance to healthy self tissues is compromised. In the face of an ipilimumab induced pan-lymphocytic activation, a therapeutic paradigm shift is required. The task is not desperately trying to put the genie back in the bottle by immune suppressive treatments, but instead harnessing the autoimmune forces by an off label low-dose combined anti-CTLA-4 and anti-PD1 antibody blockade, which is supplemented with conventional interleukin-2 stimulation and hyperthermia. The proof-of-principle of the low-dose-combination therapy was demonstrated in a heavily pre-treated triple negative breast cancer (TNBC) patient with far advanced pulmonary metastases and severe shortness of breath, who had exhausted all conventional treatment. Her pulmonary metastases went into complete remission with transient WHO I-II diarrhea and skin rash. She lived for 27 months after starting the low-dose-combination therapy. She had recurrence as a sternal mass and pleural metastases up to 3 cm. Since the low-dose-combination protocol consists only of approved drugs and treatments, this exceptional response should instigate further research efforts.

This paper examines the importance of choice of cooking fuels in wellbeing, analysing relationships between the proportion of population with primary reliance on different types of fuels for cooking (predictor variable), and key wellbeing indices (outcome variables) - Personal Health, Social Life, Civic Engagement, Life Evaluation, Negative Experience. By combining two global datasets from Gallup and WHO, the study adds to current evidence by taking a global perspective. Controlling for demographic factors such as income per capita, age, education level, employment, etc., regression modelling of these relationships show that clean cooking fuels are influential in all of the key wellbeing indices with the exception of the Life Evaluation Index. Among the key wellbeing indices, Personal Health and Negative Experience Indices are the most strongly influenced by choice of clean cooking fuels. By adding access to electricity as an additional predictor variable, the analysis highlights the potential for integrating eCooking into national electrification plans as part of sustainable energy transitions, given that health outcomes (Personal health and Negative experience indices) appear to be as closely linked to choice of cooking fuels as to access to electricity.

The rapid advancement of technology has revolutionized language learning, introducing innovative methods that depart from traditional instructional approaches. This study employs a mixed-methods research design to examine the impact of chatbot-based language learning support, adaptive learning algorithms, and virtual reality language immersion on the language learning proficiency and self-regulated learning skills of English as a Foreign Language (EFL) learners. The research design includes quantitative analysis of language proficiency scores and qualitative exploration of learner experiences with the technological interventions. The theoretical implications of this study are rooted in constructivist and socio-cultural learning theories, which underpin the design and implementation of the technological interventions. The triangulation of qualitative and quantitative data revealed that the participants' positive perceptions of the effectiveness of chatbot-based language learning support were supported by the quantitative results, with the variable "chat-bot based support" demonstrating a substantial mean difference compared to other groups. This convergence of findings reinforces the positive influence of chatbot-based support on language learning outcomes and highlights the importance of integrating theoretical perspectives with empirical evidence to gain a comprehensive understanding of the impact of technological interventions on language learning outcomes for EFL learners. The study's findings provide insights into the potential of these technological interventions to optimize language learning outcomes for EFL learners and promote autonomous learning behaviors.

Incorrect sitting posture, characterized by asymmetrical or uneven positioning of the body, often leads to spinal misalignment and muscle tone imbalance. Prolonged maintenance of such postures can adversely impact well-being and contribute to the development of spinal deformities and musculoskeletal disorders. In response, smart-sensing chairs equipped with cutting-edge sensor technologies have been introduced as a viable solution for real-time detection, classification, and monitoring of sitting postures, aiming to mitigate the risk of musculoskeletal disorders and promote overall health. This comprehensive literature review evaluates the current body of research on smart-sensing chairs, with a specific focus on the strategies used for posture detection and classification, as well as the effectiveness of different sensor technologies. A meticulous search across MDPI, IEEE, and Google Scholar databases yielded 34 pertinent studies that utilize non-invasive methods for posture monitoring. The analysis reveals that Force Sensing Resistors (FSR) are the predominant sensors utilized for posture detection, whereas Convolutional Neural Networks (CNN) and Artificial Neural Networks (ANN) are the leading machine learning models for posture classification. However, it was observed that CNNs and ANNs do not outperform traditional statistical models in terms of classification accuracy, due to constrained size and lack of diversity within training datasets. These datasets often fail to comprehensively represent the array of human body shapes and musculoskeletal configurations. Moreover, this review identifies a significant gap in the evaluation of user feedback mechanisms, essential for alerting users to their sitting posture and facilitating corrective adjustments.

Tailed phages are the most abundant and diverse group of viruses on the planet. Yet, the smallest tailed phages display relatively complex capsids and large genomes compared to other viruses. The lack of tailed phages forming the common icosahedral capsid architectures T = 1 and T = 3 is puzzling. Here, we extracted geometrical features from high-resolution tailed phage capsid reconstructions and built a statistical model based on physical principles to predict the capsid diameter and genome length of the missing small tailed phage capsids. We applied the model to 3,348 isolated tailed phage genomes and 1,496 gut metagenome-assembled tailed phage genomes. Four isolated tailed phages were predicted to form T = 3 icosahedral capsids, and twenty-one metagenome-assembled tailed phages were predicted to form T < 3 capsids. The smallest capsid predicted was a T = 4/3 ≈ 1.33 architecture. No tailed phages were predicted to form the smallest icosahedral architecture, T = 1. We discuss the feasibility of the missing T = 1 tailed phage capsids and the implications of isolating and characterizing small tailed phages for viral evolution and phage therapy.

The frequent occurrence of rib fractures in slaughtered lambs results in significant economic loss to producers and processors in South Australia and raises concerns about the welfare of the animals. The prevalence of rib fractures became evident through the Enhanced Abattoir Surveillance (EAS) program introduced in 2007. The present study aimed to investigate the association between rib fracture prevalence in lambs at slaughter and their nutrition and management on the farm of origin. The slaughter of 30,055 lambs from 60 farms was monitored at a South Australian abattoir in November 2016. Rib fracture prevalence was 4% (range 0 - 18% per consignment), with all consignments of more than 240 lambs having at least one with fractured ribs. Traceback investigation on 56 of the 60 farms suggests that rib fractures most probably occur during routine husbandry procedures and, based on soil mineral analysis, are associated with calcium inadequacy. There was substantial variation between lines of lambs from different farms, and factors contributing to the differences included line size, region, and soil characteristics, including available calcium. There is a need to modify sheep husbandry and management practices to improve sheep welfare and reduce the cost of rib fractures to the sheep industry.

Actively combating post-harvest food spoilage and waste can dramatically increase the efficiency of food utilization worldwide. In climacteric fruits, chemical treatments such as 1-MCP are an effective way of reducing post-harvest spoilage and waste by inhibiting the fruit’s ability to perceive ethylene. 1-MCP treatment is increasingly being used to explore the complex nature of ripening physiology at a fundamental level, however, differences in application and quantitation methods create difficulties in comparing conclusions across studies. Here we report an effective and reproducible method for 1-MCP application and quantitation for small-medium sized research applications. By use of surrogate alkene standards 1-butene and cis-2-butene, the highly volatile and elusive 1-MCP molecule can be identified and quantified by gas chromatography and subsequent standard curves may be developed. It is hoped that the methodology outlined here can help standardize consistent 1-MCP application for post-harvest research without excessive investment in specialized equipment.

The complexity of RNA cannot be fully expressed with the canonical A, C, G, and U alphabet. To date, over 140 distinct chemical modifications to RNA have been discovered. RNA modifications can profoundly impact the cellular outcomes of messenger RNAs (mRNAs), transfer and ribosomal RNAs, and noncoding RNAs. Additionally, aberrant RNA modifications are associated with human disease. RNA modifications are a rising topic within the fields of biochemistry and molecular biology. This review aims to provide budding scientists with an appreciation for the significance of RNA modifications, alongside the skills required to identify and fluently discuss fundamental RNA-protein interactions. The Pumilio RNA-binding protein and YT521-B homology (YTH) family of modified RNA-binding proteins serve as examples to highlight the fundamental biochemical interactions that underlie the specific recognition of both unmodified and modified ribonucleotides, respectively.

Objectives: The aim of this study was to compare the performance of the EQ-5D-Y-3L (Y-3L) and the expanded five level version, the EQ-5D-Y-5L (Y-5L). Methods: Children/adolescents with an acute or chronic health condition and from the general population completed the Y-5L and Y-3L self-report questionnaires. Performance of the Y-5L and Y-3L was determined by comparing feasibility, redistribution of dimension responses, discriminatory power, validity, and test-retest reliability. Results. Five hundred and fifty children/adolescents completed baseline measures and 173 completed repeat measures. The ceiling effect decreased by 15% from the Y-3L to Y-5L. Informativity of dimensions improved by 0.094 on the Y-5L. There was a range of 4-9% inconsistent responses moving from the Y-3L to Y-5L. Convergent validity of the Visual Analogue Scale (VAS) and Y-3L, Y-5L dimensions was similar, weak to moderate (r_s range: 0.18 – 0.38) but similar and strong on paired Y-3L and Y-5L dimensions: Kendall Tau B (range 0.69 – 0.80) and Gamma (range 0.92 – 0.98). The Y-5L and Y-3L showed moderate to substantial agreement for test-retest reliability across dimensions and VAS scores in stable chronic health conditions and fair agreement for the general population. Conclusion: The EQ-5D-Y-5L is a valid, reliable extension of the Y-3L for children/adolescents across health conditions and healthy children/adolescents. The expanded levels reduced the ceiling effect. The relative informativity of report across dimensions increased on the Y-5L compared to the Y-3L with retention of the evenness of reporting. The convergent validity and test-retest reliability of the Y-5L was comparable to the Y-3L.

The Performance Assessment for California Teachers (PACT) is a high stakes summative assessment that was designed to measure pre-service teacher readiness. We examined the inter-rater reliability (IRR) of trained PACT evaluators who rated 19 candidates. As measured by Cohen’s weighted kappa, the overall IRR estimate was .17 (poor strength of agreement). IRR estimates ranged from -.29 (worse than expected by chance) to .54 (moderate strength of agreement); all were below the standard of .70 for consensus agreement. Follow up interviews of 10 evaluators revealed possible reasons we observed low IRR, such as departures from established PACT scoring protocol, and lack of, or inconsistent, use of a scoring aid document. Evaluators reported difficulties scoring the materials that candidates submitted, particularly the use of Academic Language. Cognitive Task Analysis (CTA) is suggested as a method to improve IRR in the PACT and other teacher performance assessments such as the edTPA.

We provide a comprehensive framework for forecasting five minute load using Gaussian processes with a positive definite kernel specifically designed for load forecasts. Gaussian processes are probabilistic, enabling us to draw samples from a posterior distribution and provide rigorous uncertainty estimates to complement the point forecast, an important benefit for forecast consumers. As part of the modeling process, we discuss various methods for dimension reduction and explore their use in effectively incorporating weather data to the load forecast. We provide guidance for every step of the modeling process, from model construction through optimization and model combination. We provide results on data from the PJMISO for various periods in 2018. The process is transparent, mathematically motivated, and reproducible. The resulting model provides a probability density of five-minute forecasts for 24 hours.

Abstract—Annually, approximately 500,000 Merger and Ac- quisition (M&A) transactions are disclosed globally, each trans- action inciting substantial perturbations to the associated com- panies’ equity prices. The probability of an M&A transaction’s closure, as perceived by the public, inherently influences the stock price of the target company leading up to the proposed date of the deal. Given the recent advancements in the realm of Natural Language Processing (NLP), we propose an empirical investigation into the correlation between digital dialogue sur- rounding M&A transactions and consequent movements in the stock prices of involved companies. Utilizing transformer-based encoder-only architectures, we fine tune a stance detection model on an extensive dataset, amassed from digital communication platforms, featuring public discourse related to five historical M&A transactions. Ultimately, we achieved 70% accuracy on deal-completion stance detection using the Roberta-base model. We subsequently employ the aggregated the public sentiment towards the completion or termination of a proposed M&A transaction to model stock price movement. Utilizing a multitude of time-series based approaches, we achieve a mean absolute error of 2.29 USD for next-day price prediction and 3.40 USD for next-week price prediction. Ultimately, we find an existing but tenuous relationship between online discourse and the price trajectory of target companies, ultimately highlighting the complex social and economic phenomena behind M&A deals.Index Terms—Mergers and Acquisitions, Stock prediction, su- pervised learning, neural networks, Recurrent Neural Network, LSTM, stance detection, transformers

Background: Physical activity is recommended to mitigate the incidence of obesity, but delivery of community wide initiatives is cumbersome. The challenges met by such programs are magnified when implementation transpires in the remote villages of Alaska. To overcome the difficulty of this challenge in the Arctic, the Skiku/AK Nordic cross-country skiing program was developed. The objective of this study was to evaluate whether access to Skiku/AK Nordic program would promote physical activity levels that met the daily recommendations for physical activity in Alaska Native children. Methods: Eight children (4 females and 4 males; 10±2 years/age) were recruited from Kaktovik, Alaska for participation in this study. Expert coaches and staff provided one week of cross-country ski instruction and access to ski equipment. Physical activity was monitored using ActiGraph GT3X+ accelerometers. Data collected from the devices was then downloaded and analyzed using ActiLife software. Results: The participants expended ~586 calories/day devoted to physical activity. Light and moderate physical activity was 68±38 minutes/day and 447±248 minutes/day, respectively. Conclusions: Delivery of the Skiku/AK Nordic program promoted favorable levels of physical activity in Alaska Native children. Further research is needed to assess the longitudinal and seasonal effectiveness of the Skiku/AK Nordic program.

Introduction: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. Methods: We analyzed a large sample of data from patients with MBS (n=878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. Results: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. Conclusion: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

Viral diseases represent a major public health concern and an ever-present risk for developing into a future pandemic. Antiviral antibody therapeutics, either alone or in combination with other therapies, have emerged as valuable preventative and treatment options, including during a global emergency. Here we will discuss polyclonal and monoclonal antiviral antibody therapies, focusing on the unique biochemical and physiological properties that make them well suited as therapeutic agents. We will describe the methods of antibody characterization and potency assessment throughout development, highlighting similarities and differences between polyclonal and monoclonal products as appropriate. In addition, we will consider the benefits and challenges of antiviral antibodies when used in combination with other antibodies or other types of antiviral therapeutics. Lastly, we will discuss novel approaches to the characterization and development of antiviral antibodies and identify areas that would benefit from additional research.

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability and function. Here, we summarize these key regulatory events, with emphasis on how these affect their multi-functionality in health and disease.

Nephrolithiasis affects around 10% of the population and is frequently associated with impaired dietary factors. The first one is insufficient fluid intake inducing reduced urine volume, urine supersaturation, and subsequently urinary lithiasis. Kidneys regulate 24-hour urine volume, which, under physiological conditions, approximately reflect daily fluid intake. Increasing fluid intake has a preventive effect on the risk of developing a first kidney stone (primary prevention) but also decreases the risk of stone recurrence (secondary prevention). Current guidelines recommend increasing fluid intake at least at 2.5L /day to prevent stone formation, and even at 3.5-4L in some severe forms of nephrolithiasis (primary or enteric hyperoxaluria or cystinuria). Fluid intake must also be balanced between day and night, to avoid urinary supersaturation during the night. Patients should be informed and supported in this difficult process of increasing urine dilution, with practical ways and daily routines to increase their fluid intake. The liquid of choice is water, which should be chosen depending on its composition (such as calcium, bicarbonate or magnesium content). Finally, some additional advices have to be given to avoid some beverages such as those containing fructose or phosphoric acid, which are susceptible to increase the risk of nephrolithiasis.

Adults with obesity experience high rates of disability and rapid functional decline. Identifying movement dysfunction early can direct intervention and disrupt disability development, however subtle changes in movement are difficult to detect with the naked eye. This study evaluated how a portable, inertial measurement unit (IMU)-based motion capture system compares to a laboratory-based optokinetic motion capture (OMC) system for evaluating gait kinematics in adults with obesity. Ten adults with obesity performed overground walking while equipped with the OMC and IMU systems. Fifteen gait cycles for each participant were extracted for 150 total cycles analyzed. Kinematics were compared between OMC and IMU across the gait cycles (coefficient of multiple correlations), at clinically significant time points (interclass correlations), and over clinically relevant ranges (Bland Altman plots). Sagittal plane kinematics were most similar between systems, especially at the knee. Sagittal plane joint angles at clinically meaningful timepoints were poorly associated except for ankle dorsiflexion at heel strike (ρ=0.38) and minimum angle (ρ=0.83). Most motions had more than 5° difference between systems across the range of angles measured. IMU-based motion capture shows promise for detecting subtle gait changes in adults with obesity. However, more work is needed before this method can replace traditional OMC.

Botswana is developing its eHealth capacity using a National eHealth Strategy. However, that Strategy overlooks telemedicine, a potential solution for many healthcare challenges. For telemedicine to benefit Botswana, a telemedicine-specific strategy is required. While establishing a national strategy is a sovereign responsibility, guidance and recommendations can be provided. Using published resources specific to Botswana, key health-related issues were identified. These issues were matched with suitable telemedicine activities and delivery approaches. Recommendations were then derived from these for use in an effective telemedicine-specific strategy for Botswana. From 28 health-related issues, six were prioritised. Three telemedicine activities were identified (clinical services, education, and behaviour change), and one delivery approach was chosen (store-and-forward) because they align well with current needs, infrastructure, and mobile phone user capabilities. Since telemedicine has been proven to be effective, efficient, and cost-effective when implemented correctly this knowledge and experience, plus a recognised strategy development framework, has led to evidence-based recommendations. Specific telemedicine options were identified as examples. As confidence grows, telemedicine options can be expanded to address additional clinical needs and explore alternative activities and delivery options. The recommendations can help the Government develop a telemedicine-specific strategy that aligns with the National eHealth Strategy while actively promoting and supporting the adoption and system integration of straightforward telemedicine interventions. This foundation will facilitate the future expansion of telemedicine initiatives for the benefit of all Batswana.

This paper presents a multi-year research study conducted at the University of Toledo, aimed at improving human-machine teaming (HMT) methods and technologies. With the incorporation of artificial intelligence (AI) into 21st-century machines, collaboration between humans and machines has become highly complicated for real-time applications. The penetration of intelligent and synthetic assistants (IA/SA) in virtually every field has opened a path for the new area of HMT. When it comes to crucial tasks such as patient treatment and care, defense, and industrial production, the use of non-standardized HMT technologies may pose a risk to human lives as well as up to billions of taxpayer dollars. A thorough literature survey revealed that there are not many established standards or benchmarks for HMT. In this paper, we aim to address the lack of HMT design and development standards. We propose a method to design an HMT based on a generalized architecture. This design includes the development of an intelligent collaborative system and human team. Followed by processes and metrics to test and validate the proposed model, we present a novel human-in-the-loop (HIL) simulation method using two controlled HMT scenarios; first, emergency care provider (ECP) training, and second, patient treatment by an experienced medic. Both scenarios include humans processing visual data and performing actions that represent real-world applications while responding to a Voice-Based Synthetic Assistant (VBSA) as a collaborator that keeps track of actions. As part of these HMT simulation studies, the impact of each parameter related to machines, humans, and HMT (such as errors made by humans and by the VBSA) is presented from the perspective of performance, rules, roles, and operation limitations. In addition, based on the analysis of results from two case studies, we presented guidelines for designing future HMT. Our conclusions indicate that the proposed HIL can be used to perform standardization studies in the pursuit of developing techniques for benchmarking HMT that can be used in critical situations.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

Black spot disease is associated with the breakdown of chitin by chitinolytic bacteria resulting in extensive black lesions across the body of crustaceans. Black spot is prevalent across most fished crustaceans worldwide. Severely infected individuals are rejected from the fishery resulting in financial loss to both fisher’s and seafood export and processing companies. Ecologically, populations with high infection rates may have increased mortalities resulting in fewer individuals surviving the population. The prevalence and severity of shell disease in the edible crab, Cancer pagurus, of various size classes, was assessed via scaled images taken from crabs sampled within the Berwickshire Marine Reserve, UK. A total of 22.4% of individuals across all size groups were found to contain black spot lesions. Male crabs were more commonly affected (26.21%), with more body parts showing lesions and a greater overall blackspot coverage (1.75%) than females (16.43% and 1% respectively). Crabs under the MLS (140mm) showed a significantly higher black spot coverage, but size did not significantly affect infection rates. Carapace and chelae were the most commonly affected areas. Compared to previous studies the Berwickshire Marine Reserve has a relatively low prevalence of black spot disease in Cancer pagurus.

Background: Water treadmill (WT) exercise is a popular modality for the training and rehabilitation of horses. However, evidence-based literature regarding the use of WT exercise, particularly using inclines, is lacking.Objectives: The aim of this study was to assess the effect of recurring inclined WT sessions on equine epaxial muscles development.Methods: Six horses completed 24 sessions of 15 minutes of WT activity over four weeks. Horses walked with water at mid-cannon level at a treadmill incline of 4%. Back traces were measured at three and seven centimetres ventral to the dorsal midline at T5, T9, T14 and T18, prior to the first session (W0) and weekly for 4 weeks (W1-4). Results: Overall the back traces demonstrated progressive increases in muscle development (p<0.05), starting at W2 up to W4. At three centimetres ventral to the dorsal midline the most to least significant increases in gross muscle development were at T18, T5, T9 and T14, respectively and when measured at seven centimetres ventrally, the most to least significant increases were demonstrated at T5, T18 and T14 . It was noted that increases in thoracic back profile musculature were mainly observed within two to four weeks of the WT intervention.Conclusions: It has been concluded that repeated WT exercise on an incline setting has a significant effect on the rate and size of growth of equine thoracic back profile musculature. Muscle hypertrophy due to resistance training in the WT starts at 2 weeks within the programme, and it progresses as exercise continues to be performed.

The injury rate in agility dogs is relatively high compared to the general population. No study to date has considered the biomechanical effects of the dog walk obstacle in agility trials, highlighting a research need. The aim of this study was to test for correlation between dog age, weight, speed, contact training method and agility experience and forelimb joint angulation and peak ground reaction forces (GRFs) over this obstacle. Dogs were filmed running across a Kennel Club (KC) standard dog walk whilst wearing reflective markers attached to specific anatomical points. A Tekscan Comformat and a Tekscan Walkway pressure mat were secured to the dog walk contact area and the ground at the end of the dog walk respectively. Joint angulation and peak forelimb GRFs were recorded and analysed. A key finding is that the way a dog will move across the obstacle changes depending on their level of experience, with experienced dogs showing increased flexion of the elbow joints and decreased extension of the carpus compared to inexperienced competitors. Higher speeds over the dog walk also resulted in significantly increased elbow joint flexion. Increased joint angulation and higher GRF’s are associated with a higher risk of injury.

Coastal inundation is an increasing problem. Sea-level rise will greatly increase the frequency and depth of inundation, forcing vulnerable communities to adapt. Communities will need to decide when and how to adapt. The process of decision-making along adaptive pathways is now being used internationally to plan for adaptation over time by anticipating decision points in the future however it unfolds. This process requires risk and uncertainty considerations to be transparent in the scenarios used in such planning. We outline a framework for uncertainty identification and management within coastal hazard assessments which recognizes different types of decision and identifies the types of uncertainty that must be accounted for, such as statistical, scenario and deep uncertainty types. We show how coastal-inundation hazard can be mapped and presented in a way that clearly separates sources of uncertainty, so that they are transparent within a dynamic adaptive pathways planning process. Traditional coastal inundation maps show inundated area only. We present maps of inundation depth and frequency which clearly show the degree of exposure, where that exposure occurs, and how much sea-level rise can be tolerated. The new uncertainty framework and mapping techniques can better identify decision points and their expected time range, which provides more useful input to the adaptation process than traditional coastal inundation assessments.

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in and presents the lowest 5-year survival rate for any form of cancer in the US. Only 20% of PDAC patients are suitable for surgical resection and adjuvant chemotherapy which remains the only curative treatment. Chemotherapeutic and genetherapy treatments are associated with adverse effects and lack specificity/efficacy. In this study we assess the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP-1 or mCCL2), and mouse interleukin (mIL)-2, in human pancreatic BxPc-3 cells, using immunocompromised and CD-3+ T-cell reconstituted mice. Intratumoral treatment with TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 resulted in regression of BxPc-3 xenograft volume as compared to control in immunocompromised mice; mCCL-2 expressing TPV OV resulted in significant difference from control at p

A saprophytic soil fungus, Aspergillus flavus, produces aflatoxin (toxigenic strains) in the kernels of corn (Zea mays L.) and seeds of many other crops. Many strains of A. flavus do not produce toxigenic aflatoxin, and soil application of these atoxigenic strains is a suppressive control tactic to assist in controlling toxigenic conspecifics. Effects of atoxigenic A. flavus applications on honey bees (Apis mellifera L.) and other bees are unknown, and basic information on bee occurrences in corn fields treated with and without this biological pesticide is needed to inform integrated pest management in corn. Fields with atoxigenic A. flavus applications were compared to nearby control fields in three counties in corn production regions in eastern Texas. In each corn field, twenty bee bowl traps were deployed along four equal transects located between corn rows, with contents of the bowls (i.e. bees) retrieved after 24 hours. Eleven bee genera from four families were collected from corn fields, with only two honey bees collected and zero honey bees observed in transects. The sweat bee genus Agapostemon (primarily composed of the Texas-striped sweat bee A. texanus) was most abundant in corn fields (44% of the total number of bees collected) followed by long-horned bees (Melissodes spp., 24%). The southernmost county (i.e. San Patricio) produced over 80% of the total number of bees collected. Bee communities occurring in corn production fields with applications of atoxigenic A. flavus applications were not significantly different from nearby control fields. While little is known of bee resource use in corn production systems in Texas, the abundant yet variable bee communities across latitudes in this study suggests a need to investigate the influence of farming practices on bee resources in regional corn production systems.

The thermomechanical and viscoelastic properties of a glass fiber polyethylene terephthalate glycol (GF/PETG) continuous unidirectional (UD) tape were investigated using differential scanning calorimetry (DSC), thermo-mechanical analysis (TMA), and dynamic mechanical analysis (DMA). The study identified five operational conditions based on Army Regulation 70-38 Standard. The DSC results revealed a glass transition temperature of 78.0 ± 0.3°C, guiding the selection of temperatures for TMA and DMA tests. TMA provided the coefficient of thermal expansion in three principal directions, consistent with known values for PETG and GF materials. DMA tests, including strain sweep, temperature ramp, frequency sweep, creep, and stress relaxation, defined the linear viscoelastic region and temperature-dependent properties of the material. The frequency sweep indicated an increase in modulus with rising frequency, identifying several natural frequency modes. Creep and stress relaxation tests showed time-dependent behavior, with strain increasing under higher loads and stress decreasing over time for all tested input values. Viscoelastic models fitted to the data yielded R² values of 0.99, demonstrating good agreement. The study successfully measured thermo-mechanical and viscoelastic properties across various conditions, providing insights into how temperature influences the material's mechanical response under extreme conditions.

One in four adults in the US suffer from cartilage degeneration of the Intervertebral Disc (DDD) or load bearing joints (DJD). Combined DDD and DJD leads to billions of dollars in surgical health care costs annually. Since cartilage is avascular, it has a limited regenerative capacity. Conventional non-surgical treatment modalities provide brief symptomatic relief, have sided effects, and do not address the actual structural tissue defect in the cartilage itself. As such, new alternatives are needed. Perinatal tissue allografts have emerged as a novel frontier for bio-mechanical cartilage engineering research. Birth product-specific therapeutic roles and clinical outcomes are actively being investigated. The tissues of interest include umbilical cord-derived Wharton’s Jelly (WJ). This study assessed WJ tissue samples via ZEISS Supra 55VP Field-Emission Scanning Electron Microscope (SEM) at 100 and 300nm resolution scales. The captured images of pre and post-processed structural tissue matrices in WJ allografts were analyzed against themselves and peer-reviewed SEM images of articular cartilage, intervertebral disc cartilage, and muscle fascia. SEM images of post-processed WJ structural tissue matrices were analogous to structural tissue matrices in human articular cartilage, intervertebral disc cartilage, and muscle fascia. Relevant characteristics of pre- and post-processed structural tissue matrices in WJ allografts were comparable. This is the first study, that we are aware of, to utilize SEM to compare the pre-and post-processing relevant structural characteristics of WJ allografts and additionally demonstrate that structural collagen matrices in post-processed WJ allografts are analogous in structure to the cartilage in articular joints, intervertebral discs, and muscle fascia.

Abstract: Infectious bronchitis virus (IBV) induces respiratory and urogenital disease in chickens. Although IBV replicates in the gastrointestinal tract, enteric lesions are uncommon. We have reported a case of runting-stunting syndrome in commercial broilers from which an IBV variant was isolated from the intestines. The isolate, CalEnt, demonstrated an enteric tissue tropism in chicken embryos and SPF chickens experimentally. Here, we determined the full genome of CalEnt and compared it to other IBV strains, in addition to comparing the pathobiology of CalEnt and M41 in commercial broilers. Despite the high whole-genome identity to other IBV strains, CalEnt is rather unique in nucleotide composition. The S gene phylogenetic analyses showed great similarity between CalEnt and Cal 99. Clinically, vent staining was slightly more frequent in CalEnt-infected birds than those challenged with M41. Furthermore, IBV IHC detection was more evident and the viral shedding in feces was overall higher with the CalEnt challenge compared with M41. Despite underlying intestinal lesions caused by coccidiosis and salmonellosis vaccination, microscopic lesions in CalEnt-infected chickens were more severe than in M41-infected chickens or controls, supporting the enteric tropism of CalEnt. Further studies in SPF chickens are needed to determine the pathogenesis of the virus, its molecular mechanisms for the enteric tropism, and its influence in intestinal health.

The question of building sustainable in a geographical locality is inexorably linked to cost. In 2011, one of the authors built a sustainable house that was (at the time) the highest certified sustainable home based on the National Association of Home Builder’s standards for sustainable construction. This Texas house has been used for residential and research purposes for the past decade. In this case study, the authors evaluate components of the construction and their effectiveness as well as unseen secondary and tertiary effects. Some of the specific components discussed are home site placement; rainwater harvesting (100% of residential requirements); aerobic septic system; grid-tied solar array power; electric car charging; geothermal heating and cooling; reclaimed wood framing; spray foam installation; selection of windows, fixtures, and appliances; on-demand electric water heaters for guest areas; generator backups; and use of local items. Electric bills and water system improvements are discussed in detail, as improvements were made as part of residential and research requirements. This case study suggests that the financial outlay is worth the extra up-front costs if residents in this geographical area and climate will occupy the residence 7 years.

Background: As the opioid epidemic continues, understanding the geospatial, temporal and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis and extreme-gradient boosted random forests evaluate ICD-10 F11 opioid-related admissions and admission rates using geospatial analysis, demand analysis, and explanatory models, respectively. The period of analysis was January 2016 through September 2018. Results: The analysis shows existing high opioid admissions in Chicago and New Jersey with emerging areas in Atlanta, Salt Lake City, Phoenix, and Las Vegas. High rates of admission (claims per 10,000 population) exist in the Appalachian area and on the Northeastern seaboard. Explanatory models suggest that hospital overall workload and financial variables might be used for allocating opioid-related treatment funds effectively. Gradient-boosted random forest models accounted for 87.8% of the variability of claims on blinded 20% test data. Conclusions: Based on the GIS analysis, opioid admissions appear to have spread geographically, while higher frequency rates are still found in some regions. Interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement. Based on GIS analysis, the opioid epidemic is likely to spread or diffuse through the country, and interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement.

The human virome is an area of increasing interest with relation to human health and disease. It has been demonstrated to alter in concert with the bacterial microbiome in early life and was also found to be different in patients with certain diseases such as inflammatory bowel disease. However, all virome analyses are hampered by a lack of annotated representative database sequences, often referred to as the ‘viral dark matter’. Here we provide the first description of the gut DNA virome in elderly individuals (>65 years old) as well as the description of novel bacteriophages not present in current reference databases. Diversity analysis comparing elderly persons from different residence locations (community living vs long term care facilities) did not reveal any difference in their virome diversity profiles despite the reported differences at the bacteriome level. An abundance of Microviridae of the subfamily Gokushovirinae were present in the faeces of elderly individuals. Several novel members of the order Caudovirales were also characterized and annotated. Assignment of host bacteria to detected viral genomes was attempted using a combination of CRISPR spacers, tRNA genes and a probabilistic approach. Further characterization of the viral dark matter is necessary for developing tools and expanding databases to study the human virome. This study focused on the virome of an aging human cohort with the goal of illuminating part of the viral dark matter.

Based on surveys of winter roost sites, the eastern migratory population of the monarch butterfly (Danaus plexippus) in North America appears to have declined in the last 20 years and this has prompted the implementation of numerous conservation strategies. However, there is little information on the survivorship of first-generation monarchs in the core area of occupancy in Texas, Oklahoma, and Louisiana where overwinter population recovery begins. The purpose of this study was to determine the survivorship of first-generation eggs to third instars at a site in north Texas and to evaluate host plant arthropods for their effect on survivorship. Survivorship to third instar averaged 13.4% and varied from 11.7% to 15.6% over three years. The host plants harbored 77 arthropod taxa, including 27 predatory taxa. Despite their abundance, neither predator abundance nor predator richness predicted monarch survival. However, host plants upon which monarchs survived often harbored higher numbers of non-predatory arthropod taxa and more individuals of non-predatory taxa. These results suggest that ecological processes may have buffered the effects of predators and improved monarch survival in our study. The creation of diverse functional arthropod communities should be considered for effective monarch conservation, particularly in southern latitudes.

On Feb. 6^th, 2020, FDA implemented the enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products’ attraction to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and re-established attractions. Both the sales of e-cigarettes and posts on social media suggested that the manufacturers’ strategies are likely “successful”. The re-established attraction causes not only a public health issue, but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes that are likely added in tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco free nicotine, and these other flavors are associated with higher clinical symptoms not often induced by only natural traditional tobacco flavors. The additional health risks posed by the flavorants are pronounced even without considering the interactions of toxicology of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for regulation of these emerging products.

The human interferon-induced transmembrane (IFITM) proteins inhibit the fusion of a broad spectrum of enveloped viruses, both when expressed in target cells and when present in infected cells. Upon expression in infected cells, IFITMs incorporate into progeny virions and reduce their infectivity by a poorly understood mechanism. Since only a few Env glycoproteins are present on HIV-1 particles, and Env clustering has been proposed to be essential for optimal infectivity, we asked if IFITM protein incorporation modulates HIV-1 Env clustering. The incorporation of two members of the IFITM family, IFITM1 and IFITM3, into HIV-1 pseudoviruses verified by Western blotting correlated with a marked reduction of infectivity. Super-resolution imaging of Env distribution on single HIV-1 pseudoviruses did not reveal significant effects of IFITMs on Env clustering. However, IFITM3 markedly reduced the Env processing and incorporation into virions relative to control and IFITM1-containing viruses. These results suggest that IFITM1 and IFITM3 restrict progeny HIV-1 infectivity via distinct mechanisms. We propose that IFITM1 interferes with viral fusion by altering the properties of the viral membrane or Env functionality by means other than disrupting Env clusters, while IFITM3 also targets Env processing and incorporation into progeny virions.

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

The primary objective of this study is to report the initial efficacy data observed with the use of cryopreserved human umbilical tissue allograft for the supplementation of cartilage defects in patients with symptomatic knee osteoarthritis. Our primary endpoints were pain, stiffness, and functional recovery scores. In this ongoing study, 55 participants (age 56-93 years) received a single Wharton's jelly tissue allograft application. The study dose consisted of 150mg of Wharton's jelly allograft suspended in approximately 2mL of sterile Sodium Chloride 0.9% solution (normal saline). Each study knee application was performed under ultrasound guidance in a physician's office. The research methodology consisted of NPRS scores and WOMAC subsection scores including pain, stiffness, and physical function. Study enrollment consisted of 55 patients followed for a post-application duration of 90 days. No adverse events or adverse reactions were reported. The results demonstrated statistically significant improvements of NPRS and WOMAC in initial versus 90-day examination. The data represents Wharton's jelly tissue allograft applications are a safe, non-surgical, and efficacious for patients with symptomatic articular cartilage defects associated with osteoarthritis of the knee. 

An Environmental Decision Support System (EDSS) can be used as an important tool for rehabilitation and preservation of ecosystems. Nonetheless, high assimilation costs (both money and time) are one of the main reasons that these tools are not widely adapted in practice. This work presents a low-cost paradigm of "EDSS as a Service", this paradigm is demonstrated for developing Water Quality EDSS as a Service that utilizes the well-known CE-QUAL-W2 model as a kernel for deriving optimized decisions. The paradigm is leveraging new open-source technologies in software development (e.g. Docker, Kubernetes, and Helm) with cloud computing in order to significantly reduce assimilation costs of the EDSS for organizations and researchers working on rehabilitation and preservation of water bodies.

Memphis aquifer is the primary drinking water source in Shelby County (Tennessee, USA) and supplies industrial, commercial, and residential water. Memphis aquifer is separated from the Shallow aquifer by a clayey layer known as Upper Claiborne Confining Unit (UCCU). All of the production wells in the Memphis area are screened in the Memphis aquifer or even deeper in the Fort Pillow aquifer. Traditionally, it was assumed that the UCCU could fully protect the Memphis aquifer from the contaminated Shallow aquifer groundwater. However, recent studies show that at some locations the UCCU is thin or absent which possibly leads to the contribution of Shallow aquifer to the Memphis aquifer. Accurately locating the breaches demands expensive and difficult geological or geochemical investigations, especially within an urban area. Hence, a pre-field investigation to identify the locations where the presence of breaches is likely can significantly reduce the cost of field investigations and improve the their results. In this study, to identify the locations where the presence of breaches in the UCCU is likely we use three different analyses: (1) pilot point calibration (PPC), (2) velocity and flow budget (VFB), and (3) particle tracking (PT) to post-process the developed groundwater results. These pre-field numerical investigations provide relevant and defensible explanations for groundwater flow anomalies in an aquifer system for informed decision-making and future field investigations. In this study, we identify five specific zones within the broad study area which are reasonable candidates for the future field investigations. Finally, we test the results of each analysis against other evidence for breaches to demonstrate that the results of the numerical analyses are reliable and supported by previous studies.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.